WO2019020831A1 - Dual mode radiotracer and -therapeutics - Google Patents
Dual mode radiotracer and -therapeutics Download PDFInfo
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- WO2019020831A1 WO2019020831A1 PCT/EP2018/070533 EP2018070533W WO2019020831A1 WO 2019020831 A1 WO2019020831 A1 WO 2019020831A1 EP 2018070533 W EP2018070533 W EP 2018070533W WO 2019020831 A1 WO2019020831 A1 WO 2019020831A1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/0402—Organic compounds carboxylic acid carriers, fatty acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/0474—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group
- A61K51/0482—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group chelates from cyclic ligands, e.g. DOTA
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/0497—Organic compounds conjugates with a carrier being an organic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2121/00—Preparations for use in therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2123/00—Preparations for testing in vivo
Definitions
- ligands which are capable of binding to a disease-relevant target molecule may be cyclic peptides, such cyclic peptides are not chelating groups as envisaged herein, as the problem of the hydrophobic SIFA moiety is not solved in the absence of a further chelating moiety.
- compounds of the invention require a hydrophilic chelating group in addition to the ligands which are capable of binding to a disease-relevant target molecule.
- the hydrophilic chelating group is required to reduce the hydrophobic nature of the compounds caused by the presence of the SIFA moiety.
- radiopharmaceuticals and/or diagnostics according to the invention can be directly compared and thus will allow to link such data (e.g. data from a center in Europe working with F-18 and another center in India working with Ga-68).
- logP value (sometimes also referred to as logD value) is an art-established measure.
- the present disclosure furthermore relates to the following items.
- a macrocyclic ring structure with 8 to 20 ring atoms of which 2 or more, preferably 3 or more, are selected from oxygen atoms and nitrogen atoms;
- R 1L is CH 2 , NH or O, preferably NH;
- R 11 to R 15 are independently selected from C2 to C8 alkylene, preferably linear C2 to C8 alkylene.
- PET data (90 min acquisition time, OSEM 3D reconstruction) in blood pool (heart), muscle, kidneys, liver and LNCaP tumor xenograft of 68 Ga- nat F -8 in a
- Figure 27 Set of images of an 80 year old patient with progressive advanced castration resistant prostate cancer (PSA 66.4 ng/ml). Images shows high uptake of 18F- labelled PSMA-SIFA3 (7) in different classes of prostate cancer lesions (local tumor, lymph node metastases, bone metastases, liver metastases). Lesions demonstrated are as small as 2 mm (arrows indicate representative, not all tumor lesions).
- a proof-of-concept evaluation of use in humans was conducted under compassionate use.
- the agent was applied in compliance with The German Medicinal Products Act, AMG ⁇ 13 2b, and in accordance with the responsible regulatory body (Government of Oberbayern).
Abstract
Description
Claims
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WO2020157184A1 (en) * | 2019-01-30 | 2020-08-06 | Technische Universität München | Cancer diagnostic imaging agents |
WO2020157128A1 (en) * | 2019-01-30 | 2020-08-06 | Technische Universität München | Silicon-fluoride acceptor substituted radiopharmaceuticals and precursors thereof |
WO2020157177A1 (en) * | 2019-01-30 | 2020-08-06 | Technische Universität München | Psma binding dual mode radiotracer and therapeutic |
CN112168978A (en) * | 2019-07-03 | 2021-01-05 | 北京大学 | Antibody coupling drug, pharmaceutical composition and application thereof |
GB202108779D0 (en) | 2021-06-18 | 2021-08-04 | Blue Earth Diagnostics Ltd | Si-at therapeutic/diagnostic compounds |
GB202109922D0 (en) | 2021-07-09 | 2021-08-25 | Blue Earth Diagnostics Ltd | Radiotracers and therapeutics binding to fibroblast activation protein (fap) |
WO2021175147A1 (en) * | 2020-03-02 | 2021-09-10 | 上海核力星医药科技有限公司 | Prostate-specific membrane antigen-binding ligand conjugate and application thereof |
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WO2022018264A1 (en) | 2020-07-23 | 2022-01-27 | Technische Universität München | Silicon-containing ligand compounds |
CN114671806A (en) * | 2022-04-08 | 2022-06-28 | 上海如絮生物科技有限公司 | Hydrophilic pyridine derivative, intermediate, preparation method and application thereof |
EP4023250A1 (en) | 2021-01-04 | 2022-07-06 | Technische Universität München | Dual mode radiotracer and -therapeutics |
WO2022171901A1 (en) | 2021-02-15 | 2022-08-18 | Technische Universität München | Dual mode radiotracer and therapeutics |
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WO2023223050A1 (en) | 2022-05-19 | 2023-11-23 | Blue Earth Diagnostics Limited | Synthesis of fluorosilyl compounds |
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Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2024054226A1 (en) * | 2022-09-06 | 2024-03-14 | Hoang Ba Xuan | Gallium nitrate and dimethyl sulfoxide composition for respiratory treatment |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102626522A (en) * | 2012-04-12 | 2012-08-08 | 韩彦江 | Polypeptide radioactive diagnosis and treatment medicament based on chemotactic factor receptor CXCR4 polypeptide antagonist |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU7384394A (en) * | 1993-06-30 | 1995-01-24 | Akzo Nobel N.V. | Chelating compounds |
JP7065567B2 (en) * | 2014-06-10 | 2022-05-12 | スリービー・ファーマシューティカルズ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | Conjugates containing neurotensin receptor ligands and their use |
US20160287730A1 (en) * | 2015-03-31 | 2016-10-06 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Serv | Labeled evans blue dye derivative for in vivo serum albumin labeling |
CA2982269C (en) * | 2015-05-26 | 2023-12-05 | The Regents Of The University Of California | Heteroaromatic silicon-fluoride-acceptors useful for 18f labeling of molecules and biomolecules, and methods of preparing same |
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2022
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Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102626522A (en) * | 2012-04-12 | 2012-08-08 | 韩彦江 | Polypeptide radioactive diagnosis and treatment medicament based on chemotactic factor receptor CXCR4 polypeptide antagonist |
Non-Patent Citations (36)
Title |
---|
AFSHAR-OROMIEH ET AL., EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, vol. 42, 2015, pages 197 - 209 |
BARINKA ET AL., JOURNAL OF MEDICINAL CHEMISTRY, vol. 51, 2008, pages 7737 - 7743 |
BENESOVA ET AL., JOURNAL OF NUCLEAR MEDICINE, vol. 56, 2015, pages 914 - 920 |
BERNARD-GAUTHIER ET AL., BIOMED RES INT., vol. 2014, 2014, pages 454503 |
CARDINALE ET AL., JOURNAL OF NUCLEAR MEDICINE: OFFICIAL PUBLICATION, SOCIETY OF NUCLEAR MEDICINE, vol. 58, 2017, pages 425 - 431 |
DIETLEIN ET AL., MOLECULAR IMAGING AND BIOLOGY, vol. 17, 2015, pages 575 - 584 |
EDER ET AL., BIOCONJUGATE CHEMISTRY, vol. 23, 2012, pages 688 - 697 |
GIESEL ET AL., EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, vol. 43, 2016, pages 1929 - 1930 |
GIESEL ET AL., EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, vol. 44, 2017, pages 678 - 688 |
KIESS ET AL., THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, vol. 59, 2015, pages 241 |
LINDNER ET AL., BIOCONJUGATE CHEMISTRY, vol. 25, 2014, pages 738 - 749 |
LINDNER S. ET AL., BIOCONJUG CHEM., vol. 25, no. 4, 16 April 2014 (2014-04-16), pages 738 - 49 |
LIU ET AL., BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 21, 2011, pages 7013 - 7016 |
LOVKOVA ET AL., CHEMISTRY, vol. 15, 2009, pages 2140 - 7 |
MACHULKIN ET AL., JOURNAL OF DRUG TARGETING, vol. 1-15, 2016 |
MAURER ET AL., NATURE REVIEWS UROLOGY, 2016 |
NIEDERMOSER S. ET AL., J NUCL MED., vol. 56, no. 7, July 2015 (2015-07-01), pages 1100 - 5 |
NOTNI ET AL., CHEMISTRY, vol. 16, 2010, pages 7174 - 85 |
NOTNI ET AL., EJNMMI RESEARCH, vol. 28, 2012 |
REICH ET AL., CHEMICAL COMMUNICATIONS, vol. 53, 2017, pages 2586 - 2589 |
ROBU ET AL., JOURNAL OF NUCLEAR MEDICINE, JNUMED., vol. 116.1789, 2016 |
ROWE ET AL., MOLECULAR IMAGING AND BIOLOGY, 2016, pages 1 - 9 |
ROWE ET AL., PROSTATE CANCER AND PROSTATIC DISEASES, 2016 |
S. LITAU ET AL: "Next Generation of SiFA lin -Based TATE Derivatives for PET Imaging of SSTR-Positive Tumors: Influence of Molecular Design on In Vitro SSTR Binding and In Vivo Pharmacokinetics", BIOCONJUGATE CHEMISTRY, vol. 26, no. 12, 16 December 2015 (2015-12-16), pages 2350 - 2359, XP055452403, ISSN: 1043-1802, DOI: 10.1021/acs.bioconjchem.5b00510 * |
SANGSTER: "Octanol-water Partition Coefficients: fundamentals and physical chemistry", 1997, JOHN WILEY & SONS |
SCHIRRMACHER E. ET AL., BIOCONJUGATE CHEM., vol. 18, 2007, pages 2085 - 2089 |
SILVER ET AL., CLINICAL CANCER RESEARCH, vol. 3, 1997, pages 81 - 85 |
SIMON LINDNER ET AL: "Synthesis and in Vitro and in Vivo Evaluation of SiFA-Tagged Bombesin and RGD Peptides as Tumor Imaging Probes for Positron Emission Tomography", BIOCONJUGATE CHEMISTRY, vol. 25, no. 4, 16 April 2014 (2014-04-16), pages 738 - 749, XP055449461, ISSN: 1043-1802, DOI: 10.1021/bc400588e * |
VADIM BERNARD-GAUTHIER ET AL: "From Unorthodox to Established: The Current Status of 18 F-Trifluoroborate- and 18 F-SiFA-Based Radiopharmaceuticals in PET Nuclear Imaging", BIOCONJUGATE CHEMISTRY, vol. 27, no. 2, 17 February 2016 (2016-02-17), pages 267 - 279, XP055305200, ISSN: 1043-1802, DOI: 10.1021/acs.bioconjchem.5b00560 * |
WANGLER C. ET AL., BIOCONJUG CHEM., vol. 21, no. 12, 15 December 2010 (2010-12-15), pages 2289 - 96 |
WANGLER C. ET AL., BIOCONJUGATE CHEM., vol. 20, no. 2, 2009, pages 317 - 321 |
WANGLER ET AL., NAT PROTOC, vol. 7, 2012, pages 1946 - 55 |
WEINEISEN ET AL., EJNMMI RESEARCH, vol. 4, 2014, pages 63 |
WEINEISEN ET AL., JOURNAL OF NUCLEAR MEDICINE, vol. 55, 2014, pages 1083 - 1083 |
ZHANG ET AL., JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 132, 2010, pages 12711 - 12716 |
ZHOU ET AL., NATURE REVIEWS DRUG DISCOVERY, vol. 4, 2005, pages 1015 - 1026 |
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